DOI QR코드

DOI QR Code

Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms and Breast Cancer Risk in a Chinese Population

  • Luo, Ting (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Chen, Long (Department of Laboratory Medicine, West China Hospital, Sichuan University) ;
  • He, Ping (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Hu, Qian-Cheng (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Zhong, Xiao-Rong (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Sun, Yu (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Yang, Yuan-Fu (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Tian, Ting-Lun (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University) ;
  • Zheng, Hong (Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center and State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University)
  • 발행 : 2013.04.30

초록

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.

참고문헌

  1. 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
  2. Belinsky GS, Claffey KP, Nambiar PR, et al (2005). Vascular endothelial growth factor and enhanced angiogenesis do not promote metastatic conversion of a newly established azoxymethane-induced colon cancer cell line. Mol Carcinog, 43, 65-74. https://doi.org/10.1002/mc.20079
  3. Dassoulas K, Gazouli M, Rizos S, et al (2009). Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival. Mol Carcinog, 48, 563-9. https://doi.org/10.1002/mc.20495
  4. 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
  5. Ferrara N (2002). VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2, 795-803. https://doi.org/10.1038/nrc909
  6. Ferrara N, Gerber HP, LeCouter J (2003). The biology of VEGF and its receptors. Nat Med, 9, 669-76. https://doi.org/10.1038/nm0603-669
  7. Garcia-Closas M, Malats N, Real FX, et al (2007). Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk. PLoS Genet, 3, e29. https://doi.org/10.1371/journal.pgen.0030029
  8. Gu D, Wang M (2011). VEGF 936C>T polymorphism and breast cancer risk: evidence from 5,729 cases and 5,868 controls. Breast Cancer Res Treat, 125, 489-93. https://doi.org/10.1007/s10549-010-0991-z
  9. Iordache S, Saftoiu A, Georgescu CV, et al (2010). Vascular endothelial growth factor expression and microvessel density-two useful tools for the assessment of prognosis and survival in gastric cancer patients. J Gastrointestin Liver Dis, 19, 135-9.
  10. 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, R22. https://doi.org/10.1186/bcr1400
  11. 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
  12. 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
  13. Jin B, Jiang F, Ding Z (2011). Revaluation of the association between vascular endothelial growth factor gene 936 C/T polymorphism and breast cancer risk. Breast Cancer Res Treat, 128, 909-12. https://doi.org/10.1007/s10549-011-1439-9
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. Liu L, Hua FZ, Cao JQ, et al (2011). VEGF 936C>T polymorphism and breast cancer risk: evidence needed further clarification. Breast Cancer Res Treat, 127, 569-71. https://doi.org/10.1007/s10549-010-1339-4
  20. 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
  21. 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
  22. Perrone G, Vincenzi B, Santini D, et al (2004). Correlation of p53 and bcl-2 expression with vascular endothelial growth factor (VEGF), microvessel density (MVD) and clinicopathological features in colon cancer. Cancer Lett, 208, 227-34. https://doi.org/10.1016/j.canlet.2003.11.032
  23. Qiu LX, Wang K, Yang S, et al (2011). Current evidences on vascular endothelial growth factor polymorphisms and breast cancer susceptibility. Mol Biol Rep, 38, 4491-4. https://doi.org/10.1007/s11033-010-0579-z
  24. 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
  25. 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
  26. Ronco AL, De Stefani E, Deneo-Pellegrini H (2012a). Risk factors for premenopausal breast cancer: a case-control study in Uruguay. Asian Pac J Cancer Prev, 13, 2879-86. https://doi.org/10.7314/APJCP.2012.13.6.2879
  27. Ronco AL, De Stefani E, Deneo-Pellegrini H, et al (2012b). Diabetes, overweight and risk of postmenopausal breast cancer: a case-control study in Uruguay. Asian Pac J Cancer Prev, 13, 139-46. https://doi.org/10.7314/APJCP.2012.13.1.139
  28. 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
  29. Schneider BP, Wang M, Radovich M, et al (2008). Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol, 26, 4672-8. https://doi.org/10.1200/JCO.2008.16.1612
  30. Shamsi U, Khan S, Usman S, et al (2013). A multicenter matched case control study of breast cancer risk factors among women in Karachi, Pakistan. Asian Pac J Cancer Prev, 14, 183-8. https://doi.org/10.7314/APJCP.2013.14.1.183
  31. Stefanou D, Batistatou A, Kamina S, et al (2004). Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in benign prostatic hyperplasia and prostate cancer. In Vivo, 18, 155-60.
  32. Sun JW, Li XR, Gao HY, et al (2013). Electromagnetic Field Exposure and Male Breast Cancer Risk: A Meta-analysis of 18 Studies. Asian Pac J Cancer Prev, 14, 523-8. https://doi.org/10.7314/APJCP.2013.14.1.523
  33. Vincenti V, Cassano C, Rocchi M, et al (1996). Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation, 93, 1493-5. https://doi.org/10.1161/01.CIR.93.8.1493
  34. Wang K, Li X, Zhou C, et al (2013). Socio-economic Factors Influencing Tumor Presentation and Treatment Options in Chinese Breast Cancer Patients. Asian Pac J Cancer Prev, 14, 267-74. https://doi.org/10.7314/APJCP.2013.14.1.267
  35. Wang K, Liu L, Zhu ZM, et al (2011). Five polymorphisms of vascular endothelial growth factor (VEGF) and risk of breast cancer: a meta-analysis involving 16,703 individuals. Cytokine, 56, 167-73. https://doi.org/10.1016/j.cyto.2011.06.018
  36. Wang K, Peng HL, Li LK (2012). Prognostic value of vascular endothelial growth factor expression in patients with prostate cancer: a systematic review with meta-analysis. Asian Pac J Cancer Prev, 13, 5665-9. https://doi.org/10.7314/APJCP.2012.13.11.5665
  37. 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
  38. Wehrschuetz M, Schollnast H, Wehrschuetz E, et al (2009). VEGF 936C > T polymorphism and association of BI-RADS score in women with suspected breast cancer. Breast Cancer (Auckl), 3, 77-81.
  39. Yang DS, Park KH, Woo OH, et al (2011). Association of a vascular endothelial growth factor gene 936 C/T polymorphism with breast cancer risk: a meta-analysis. Breast Cancer Res Treat, 125, 849-53. https://doi.org/10.1007/s10549-010-1070-1
  40. Zhang YF, Kang HB, Li BL, et al (2012). Positive effects of soy isoflavone food on survival of breast cancer patients in China. Asian Pac J Cancer Prev, 13, 479-82. https://doi.org/10.7314/APJCP.2012.13.2.479
  41. Zhou LP, Luan H, Dong XH, et al (2012a). Association between XRCC5, 6 and 7 gene polymorphisms and the risk of breast cancer: a HuGE review and meta-analysis. Asian Pac J Cancer Prev, 13, 3637-43. https://doi.org/10.7314/APJCP.2012.13.8.3637
  42. Zhou P, Huang W, Chu X, et al (2012b). The lymphotoxin-alpha 252A>G polymorphism and breast cancer: a meta-analysis. Asian Pac J Cancer Prev, 13, 1949-52. https://doi.org/10.7314/APJCP.2012.13.5.1949
  43. Zhou Y, Li N, Zhuang W, et al (2011). Vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk in a Chinese Han population. Mol Carcinog, 50, 184-8. https://doi.org/10.1002/mc.20703

피인용 문헌

  1. Expression and Significance of ER, PR, VEGF, CA15-3, CA125 and CEA in Judging the Prognosis of Breast Cancer vol.14, pp.6, 2013, https://doi.org/10.7314/APJCP.2013.14.6.3937
  2. Association of +405C>G and +936C>T Polymorphisms of the Vascular Endothelial Growth Factor Gene with Sporadic Breast Cancer in North Indians vol.15, pp.1, 2014, https://doi.org/10.7314/APJCP.2014.15.1.257
  3. The −1154 G/A VEGF gene polymorphism is associated with the incidence of basal cell carcinoma in patients from northern Poland vol.306, pp.6, 2014, https://doi.org/10.1007/s00403-014-1471-9
  4. The association of SIPA1 gene polymorphisms with breast cancer risk: evidence from published studies vol.35, pp.1, 2014, https://doi.org/10.1007/s13277-013-1061-z
  5. Vascular endothelial growth factor +936C/T polymorphism and breast cancer risk: a meta-analysis of 13 case–control studies vol.35, pp.3, 2014, https://doi.org/10.1007/s13277-013-1354-2
  6. Vascular endothelial growth factor gene polymorphism (-634G/C) and breast cancer risk vol.35, pp.8, 2014, https://doi.org/10.1007/s13277-014-1997-7
  7. Predictive value of vascular endothelial growth factor polymorphisms on the clinical outcome of renal cell carcinoma patients pp.1792-1082, 2014, https://doi.org/10.3892/ol.2014.2798
  8. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma vol.10, pp.12, 2015, https://doi.org/10.1371/journal.pone.0145410
  9. Prognostic and predictive role of vascular endothelial growth factor polymorphisms in breast cancer vol.16, pp.1, 2015, https://doi.org/10.2217/pgs.14.148
  10. Association between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population vol.10, pp.1178-2234, 2016, https://doi.org/10.4137/BCBCR.S39649
  11. Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer vol.17, pp.6, 2016, https://doi.org/10.1080/15384047.2016.1190486
  12. Haplotype-based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population pp.08878013, 2018, https://doi.org/10.1002/jcla.22610