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Association of +405C>G and +936C>T Polymorphisms of the Vascular Endothelial Growth Factor Gene with Sporadic Breast Cancer in North Indians

  • Kapahi, Ruhi (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University) ;
  • Manjari, Mridu (Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Sudan, Meena (Department of Radiotherapy, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Uppal, Manjit Singh (Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Singh, Neeti Rajan (Department of Surgery, Sri Guru Ram Das Institute of Medical Sciences and Research) ;
  • Sambyal, Vasudha (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University) ;
  • Guleria, Kamlesh (Human Cytogenetics Laboratory, Department of Human Genetics, Guru Nanak Dev University)
  • Published : 2014.01.15

Abstract

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.

Keywords

References

  1. Adeli K, Ogbonna G (1990). Rapid purification of human DNA from whole blood for potential application in clinical chemistry laboratories. Clin Chem, 36, 261-4.
  2. Bae SJ, Ahn DH, Hong SP, et al (2008). Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936C>T) gene and patients with stomach cancer. Yonsei Med J, 49, 783-91. https://doi.org/10.3349/ymj.2008.49.5.783
  3. Balasubramanian SP, Cox A, Cross SS, et al (2007). Influence of VEGF-A gene variation and protein levels in breast cancer susceptibility and severity. Int J Cancer, 121, 1009-16. https://doi.org/10.1002/ijc.22772
  4. Bao G, Wang M, Guo S, et al (2011). Vascular endothelial growth factor +936 C/T gene polymorphism and glioma risk in a Chinese Han population. Genet Test Mol Biomarkers, 15, 103-6. https://doi.org/10.1089/gtmb.2010.0141
  5. Bastide A, Karaa Z, Bornes S, et al (2008). An upstream open reading frame within an IRES controls expression of a specific VEGF-A isoform. Nucleic Acids Res, 36, 2434-45. https://doi.org/10.1093/nar/gkn093
  6. Bhanoori M, Arvind Babu K, Pavankumar Reddy NG, et al (2005). The vascular endothelial growth factor (VEGF) +405G>C 5'-untranslated region polymorphism and increased risk of endometriosis in South Indian women: a case control study. Hum Reprod, 20, 1844-9. https://doi.org/10.1093/humrep/deh852
  7. Blackwood MA, Weber BL (1998). BRCA1 and BRCA2: from molecular genetics to clinical medicine. J Clin Oncol, 16, 1969-77.
  8. Breast cancer facts and figures 2011-2012. http://www.cancer.org/research/cancerfactsstatistics/index. Accessed 9 September 2013
  9. Carmeliet P (2005). VEGF as a key mediator of angiogenesis in cancer. Oncol, 69, 4-10. https://doi.org/10.1159/000088478
  10. Chae YS, Kim JG, Sohn SK, et al (2006). Investigation of vascular endothelial growth factor gene polymorphisms and its association with clinicopathologic characteristics in gastric cancer. Oncol, 71, 266-72. https://doi.org/10.1159/000106788
  11. Chae YS, Kim JG, Sohn SK, et al (2008). Association of vascular endothelial growth factor gene polymorphisms with susceptibility and clinicopathologic characteristics of colorectal cancer. J Korean Med Sci, 23, 421-7. https://doi.org/10.3346/jkms.2008.23.3.421
  12. Cooke RW, Drury JA, Mountford R, (2004). Genetic polymorphisms and retinopathy of prematurity. Invest Ophthalmol Vis Sci, 45, 1712-5. https://doi.org/10.1167/iovs.03-1303
  13. Eroglu A, Ozturk A, Cam R, et al (2008). Vascular endothelial growth factor gene 936 C/T polymorphism in breast cancer patients. Med Oncol, 25, 54-5. https://doi.org/10.1007/s12032-007-0046-4
  14. Ferlay J, Shin HR, Bray F, et al (2008). GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. Lyon, France: International Agency for Research on Cancer; 2010.
  15. Folkman J (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol, 29, 15-8.
  16. Gentilini D, Somigliana E, Vigano P, et al (2008). The vascular endothelial growth factor +405G>C polymorphism in endometriosis. Hum Reprod, 23, 211-5.
  17. Gerger A, Langsenlehner U, Renner W, et al (2007). A multigenic approach to predict breast cancer risk. Breast Cancer Res Treat, 104, 159-64. https://doi.org/10.1007/s10549-006-9408-4
  18. Guan X, Zhao H, Niu J, et al (2009). The VEGF-634G>C promoter polymorphism is associated with risk of gastric cancer. BMC Gastroenterol, 9, 77 https://doi.org/10.1186/1471-230X-9-77
  19. Hamedian AA, Esteghamati A, Noshad S, et al (2012). Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran. Mol Biol Rep, 39, 6213-8. https://doi.org/10.1007/s11033-011-1440-8
  20. Hefler LA, Mustea A, Konsgen D, et al (2007). Vascular endothelial growth factor gene polymorphisms are associated with prognosis in ovarian cancer. Clin Cancer Res, 13, 898-901. https://doi.org/10.1158/1078-0432.CCR-06-1008
  21. Hicklin DJ, Ellis LM (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol, 23, 1011-27.
  22. Huez I, Bornes S, Bresson D, Creancier L, Prats H (2001). New vascular endothelial growth factor isoform generated by internal ribosome entry site-driven CUG translation initiation. Mol Endocrinol, 15, 2197-210. https://doi.org/10.1210/mend.15.12.0738
  23. Ishigami SI, Arii S, Furutani M, et al (1998). Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer. Br J Cancer, 78, 1379-84. https://doi.org/10.1038/bjc.1998.688
  24. Jacobs EJ, Feigelson HS, Bain EB, et al (2006). Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Res, 8, 22.
  25. Jain L, Vargo CA, Danesi R, et al (2009). The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors. Mol Cancer Ther, 8, 2496-508. https://doi.org/10.1158/1535-7163.MCT-09-0302
  26. Jakubowska A, Gronwald J, Menkiszak J, et al (2008). The VEGF +936 C>T 3'UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women. Cancer Lett, 262, 71-6. https://doi.org/10.1016/j.canlet.2007.11.029
  27. Jemal A, Bray F, Center, MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  28. Jin Q, Hemminki K, Enquist K, et al (2005). Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res, 11, 3647-53. https://doi.org/10.1158/1078-0432.CCR-04-1803
  29. Kariyazono H, Ohno T, Khajoee V, 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, 953-9. https://doi.org/10.1203/01.PDR.0000145280.26284.B9
  30. Kataoka N, Cai Q, Wen W, et al (2006). Population-based casecontrol study of VEGF gene polymorphisms and breast cancer risk among Chinese women. Cancer Epidemiol Biomarkers Prev, 15, 1148-52. https://doi.org/10.1158/1055-9965.EPI-05-0871
  31. Kawakami M, Furuhata T, Kimura Y, et al (2003). Expression analysis of vascular endothelial growth factors and their relationships to lymph node metastasis in human colorectal cancer. J Exp Clin Cancer Res, 22, 229-37.
  32. Kerbel RS (2008). Tumor angiogenesis. N Engl J Med, 358, 2039-49. https://doi.org/10.1056/NEJMra0706596
  33. Kim JG, Sohn SK, Chae YS, et al (2007). Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with gastric cancer. Ann Oncol, 18, 1030-6. https://doi.org/10.1093/annonc/mdm085
  34. Koukourakis MI, Papazoglou D, Giatromanolaki A, et al (2004). VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer, 46, 293-8. https://doi.org/10.1016/j.lungcan.2004.04.037
  35. Krippl P, Langsenlehner U, Renner W, 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, 468-71. https://doi.org/10.1002/ijc.11238
  36. Lachheb J, Chelbi H, Ben Dhifallah I, et al (2008). Association of vascular endothelial growth factor polymorphisms with asthma in Tunisian children. Gene Regul Syst Bio, 2, 89-96.
  37. Langsenlehner U, Wolf G, Langsenlehner T, 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. https://doi.org/10.1007/s10549-007-9655-z
  38. Lee SJ, Lee SY, Jeon HS, et al (2005). Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev, 14, 571-5. https://doi.org/10.1158/1055-9965.EPI-04-0472
  39. Lu H, Shu XO, Cui Y, et al (2005). Association of genetic polymorphisms in the VEGF gene with breast cancer survival. Cancer Res, 65, 5015-9. https://doi.org/10.1158/0008-5472.CAN-04-2786
  40. Luo T, Chen L, He P, et al (2013). Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in a Chinese population. Asian Pac J Cancer Prev, 14, 2433-7. https://doi.org/10.7314/APJCP.2013.14.4.2433
  41. Maltese P, Canestrari E, Ruzzo A, et al (2009). VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population. Int J Colorectal Dis, 24, 165-70. https://doi.org/10.1007/s00384-008-0586-x
  42. Miki Y, Swensen J, Shattuck-Eidens D, et al (1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science, 266, 66-71. https://doi.org/10.1126/science.7545954
  43. Morabito A, Sarmiento R, Bonginelli P, et al (2004). Antiangiogenic strategies, compounds, and early clinical results in breast cancer. Crit Rev Oncol Hematol, 49, 91-107. https://doi.org/10.1016/S1040-8428(03)00168-9
  44. Naik NA, Bhat IA, Afroze D, et al (2012). Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India). Tumor Biol, 33, 833-9. https://doi.org/10.1007/s13277-011-0306-y
  45. Nathanson KL, Weber BL (2001). "Other" breast cancer susceptibility genes: searching for more holy grail. Hum Mol Genet, 10, 715-20. https://doi.org/10.1093/hmg/10.7.715
  46. Nikzamir A, Esteghamati A, Hammedian AA, et al (2012). The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus. Mol Biol Rep, 39, 881-6. https://doi.org/10.1007/s11033-011-0812-4
  47. Oliveira C, Lourenco GJ, Silva PM, et al (2011). Polymorphisms in the 5'-and 3'-untranslated region of the VEGF gene and sporadic breast cancer risk and clinicopathologic characteristics. Tumour Biol, 32, 295-300. https://doi.org/10.1007/s13277-010-0121-x
  48. Peyromaure M, Camparo P, Badoual C, et al (2007).The expression of vascular endothelial growth factor is associated with the risk of cancer progression after radical Prostatectomy. BJU Int, 99, 1150-3. https://doi.org/10.1111/j.1464-410X.2007.06734.x
  49. Pharoah PD, Antoniou A, Bobrow M, et al (2002). Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet, 31, 33-6. https://doi.org/10.1038/ng853
  50. Ponder BA (2001). Cancer genetics. Nature, 411, 336-41. https://doi.org/10.1038/35077207
  51. Renner W, Kotschan S, Hoffmann C, et al (2000). 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, 37, 443-8. https://doi.org/10.1159/000054076
  52. Rodrigues P, Furriol J, Tormo, E, et al (2012). The singlenucleotide polymorphisms +936 C/T VEGF and-710 C/T VEGFR1 are associated with breast cancer protection in a Spanish population. Breast Cancer Res Treat, 133, 769-78. https://doi.org/10.1007/s10549-012-1980-1
  53. Roy H, Bhardwaj S, Yla-Herttuala S (2006). Biology of vascular endothelial growth factors. FEBS Lett, 580, 2879-87. https://doi.org/10.1016/j.febslet.2006.03.087
  54. Ruzzo A, Graziano F, Kawakami K, et al (2006). Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy. J Clin Oncol, 24, 1883-91. https://doi.org/10.1200/JCO.2005.04.8322
  55. Schneider BP, Radovich M, Sledge GW, et al (2008). Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat, 111, 157-63. https://doi.org/10.1007/s10549-007-9755-9
  56. Schoppmann SF, Horvat R, Birner P (2002). Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical impact and possible implications for antilymphangiogenic therapies (Review). Oncol Rep, 9, 455-60.
  57. Sfar S, Hassen E, Saad H, et al (2006). Association of VEGF genetic polymorphisms with Prostate carcinoma risk and clinical outcome. Cytokine, 35, 21-8. https://doi.org/10.1016/j.cyto.2006.07.003
  58. Sivaprasad S, Govardhan B, Harithakrishna R, et al (2013). Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma. Pancreatol, 13, 267-72. https://doi.org/10.1016/j.pan.2013.02.006
  59. Stevens A, Soden J, Brenchley PE, et al (2003). Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter. Cancer Res, 63, 812-6.
  60. Talar-Wojnarowska R, Gasiorowska A, Olakowski M, et al (2010). Vascular endothelial growth factor (VEGF) genotype and serum concentration in patients with pancreatic adenocarcinoma and chronic pancreatitis. J Physiol Pharmacol, 61, 711-6.
  61. Tischer E, Mitchell R, Hartman T, et al (1991). The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem, 266, 11947-54.
  62. Tzanakis N, Gazouli M, Rallis G, et al (2006). Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol, 94, 624-30. https://doi.org/10.1002/jso.20619
  63. Watson CJ, Webb NJ, Bottomley MJ, et al (2000). Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine, 12, 1232-5. https://doi.org/10.1006/cyto.2000.0692
  64. Wolf G, Aigner RM, Schaffler G, et al (2004). The 936C>T polymorphism of the gene for vascular endothelial growth factor is associated with 18F-fluorodeoxyglucose uptake. Breast Cancer Res Treat, 88, 205-8. https://doi.org/10.1007/s10549-004-0724-2
  65. Wooster R, Bignell G, Lancaster J, et al (1995). Identification of the breast cancer susceptibility gene BRCA2. Nature, 378, 789-92. https://doi.org/10.1038/378789a0
  66. Yapijakis C, Vairaktaris E, Vassiliou S, et al (2007). The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer. J Cancer Res Clin Oncol, 133, 787-91. https://doi.org/10.1007/s00432-007-0240-y
  67. Zhai R, Liu G, Zhou W, et al (2008a). Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer. Clin Cancer Res, 14, 612-7. https://doi.org/10.1158/1078-0432.CCR-07-1655
  68. Zhai R, Liu G, Asomaning K, et al (2008b). Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. Carcinogenesis, 29, 2330-4. https://doi.org/10.1093/carcin/bgn210
  69. Zhang B, Beeghly-Fadiel A, Lu W, et al (2011). Evaluation of functional genetic variants for breast cancer risk: results from the Shanghai breast cancer study. Am J Epidemiol, 173, 1159-70. https://doi.org/10.1093/aje/kwr004
  70. Zhao Z, Fu YX, Hewett-Emmett D, et al (2003). Investigating single nucleotide polymorphism (SNP) density in the human genome and its implications for molecular evolution. Gene, 312, 207-13. https://doi.org/10.1016/S0378-1119(03)00670-X

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