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Germ-line MTHFR C677T, FV H1299R and PAI-1 5G/4G Variations in Breast Carcinoma

  • Ozen, Filiz (Department of Medical Genetics, Faculty of Medicine, Cumhuriyet University) ;
  • Erdis, Eda (Department of General Surgery, Faculty of Medicine, Cumhuriyet University) ;
  • Sik, Ebru (Department of Medical Genetics, Faculty of Medicine, Canakkale Onsekiz Mart University) ;
  • Silan, Fatma (Department of Medical Genetics, Faculty of Medicine, Canakkale Onsekiz Mart University) ;
  • Uludag, Ahmet (Department of Medical Genetics, Faculty of Medicine, Canakkale Onsekiz Mart University) ;
  • Ozdemir, Ozturk (Department of Medical Genetics, Faculty of Medicine, Cumhuriyet University)
  • Published : 2013.05.30

Abstract

Background: Various oncogenes related to cancer have been extensively studied and several polymorphisms have been found to be associated with breast cancer. The current report outlines analysis of germ-line polymorphisms for C677T, A1298C (MTHFR), Leiden, R2 (FV) and 5G/4G (PAI-1) in Turkish breast cancer patients. We studied 51 cases diagnosed with invasive ductal and operable with lymph node-positive breast cancer and 106 women as a control group. Materials and Methods: Peripheric blood-DNA samples were used for genotyping by StripAssay technique which is based on the reverse-hybridization principle and real-time PCR methods and results were compared statistically. Results: The frequency of the MTHFR gene 677T and 1298A alleles were significantly higher in cancer patients than in the healthy subjects. The T allele frequency in codon 677 was 2.3-fold and C allele frequency was 3.1-fold increased in BC when compared to the control group for the MTHFR gene. Both differences were statistically significant (OR: 2.295, CI: 1.283-4.106), p<0.006 and (OR: 3.131, CI:1.826-5.369), p<0.0001 respectively. The R2 allele frequency of FV gene was 5.1-fold increased in the current BC when compared to the control group and that difference was also statistically significant (OR: 5.133, CI: 1.299-20.28), p<0.02. Conclusions: The present data suggest that germ-line polymorphisms of C677T, C1298A for MTHFR and R2 for FV are associated in breast cancer and may be additional prognostic markers related to breast cancer survival. The results now need to be confirmed in a larger group of patients.

Keywords

MTHFR C677T and A1298C;FV Leiden and R2;PAI-1 5G/4G;SNPs;breast carcinoma

References

  1. Akbari M, Donenberg T, Lunn J, et al (2013). The spectrum of BRCA1 and BRCA2 mutations in breast cancer patients in the Bahamas. Clin Genet. [Epub ahead of print].
  2. Akram M, Malik FA, Kayani MA (2012).Mutational analysis of the MTHFR gene in breast cancer patients of Pakistani population. Asian Pac J Cancer Prev. 13, 1599-603. https://doi.org/10.7314/APJCP.2012.13.4.1599
  3. Bhar A, Haubrock M, Mukhopadhyay A, et al (2013). Coexpression and coregulation analysis of time-series gene expression data in estrogen-induced breast cancer cell. Algorithms Mol Biol, 8, 9. https://doi.org/10.1186/1748-7188-8-9
  4. Bonache S, de la Hoya M, Gutierrez-Enriquez S, et al (2013). Mutation analysis of the SHFM1 gene in breast/ovarian cancer families. J Cancer Res Clin Oncol, 139, 529-32. https://doi.org/10.1007/s00432-013-1385-5
  5. Carraro DM, Koike Folgueira MA, Garcia Lisboa BC, et al (2013). Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: A Portrait of Early-Onset Breast Cancer in Brazil. PLoS One, 8, 57581. https://doi.org/10.1371/journal.pone.0057581
  6. Chang S, Sharan SK (2012).The role of epigenetic transcriptional regulation in BRCA1-mediated tumor suppression. Transcription, [Epub ahead of print].
  7. de Cassia Carvalho Barbosa R, da Costa DM, Cordeiro DE, et al (2012). Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil. Anticancer Res, 32, 4805-811.
  8. Descotes F, Riche B, Saez S, et al (2008).Plasminogen activator inhibitor type 1 is the most significant of the usual tissue prognostic factors in node-negative breast ductal adenocarcinoma independent of urokinase-type plasminogen activator. Clin Breast Cancer, 8, 168-77. https://doi.org/10.3816/CBC.2008.n.018
  9. Diakite B, Tazzite A, Hamzi K, et al (2012). Methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Moroccan women. Afr Health Sci, 12, 204-9.
  10. Eljuga D, Razumovic JJ, Bulic K, et al (2011). Prognostic importance of PAI-1 in node negative breast cancer patients--results after 10 years of follow up. Pathol Res Pract, 207, 290-4. https://doi.org/10.1016/j.prp.2011.02.008
  11. Ericson U, Sonestedt E, Ivarsson MI, et al (2009). Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the malmo diet and cancer cohort. Cancer Epidemiol Biomarkers Prev, 18,1101-10. https://doi.org/10.1158/1055-9965.EPI-08-0401
  12. Eroglu A, Akar N (2010). Methylenetetrahydrofolate reductase C677T polymorphism in breast cancer risk. Breast Cancer Res Treat, 122, 897-8. https://doi.org/10.1007/s10549-010-0938-4
  13. Eroglu A, Akar N (2011). Factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms and the risk of tamoxifenassociated thromboembolism in breast cancer patients. Thromb Res, 127, 384-5. https://doi.org/10.1016/j.thromres.2010.10.025
  14. Fersching DM, Nagel D, Siegele B, et al (2012).Apoptosisrelated biomarkers sFAS, MIF, ICAM-1 and PAI-1 in serum of breast cancer patients undergoing neoadjuvant chemotherapy. Anticancer Res, 32, 2047-58.
  15. Gao CM, Tang JH, Cao HX, et al (2009). MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women. J Hum Genet, 54, 414-8. https://doi.org/10.1038/jhg.2009.57
  16. Henriquez-Hernandez LA, Murias-Rosales A, Gonzalez-Hernandez A, et al (2010). Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. Cancer Epidemiol, 34, 634-38. https://doi.org/10.1016/j.canep.2010.06.013
  17. Hildenbrand R, Schaaf A, Dorn-Beineke A, et al (2009). Tumor stroma is the predominant uPA-, uPAR-, PAI-1-expressing tissue in human breast cancer: prognostic impact. Histol Histopathol, 24, 869-77.
  18. Hosseini M, Houshmand M, Ebrahimi A (2011). MTHFR polymorphisms and breast cancer risk. Arch Med Sci, 7, 134-7.
  19. Jelisavac-Cosic S, Sirotkovic-Skerlev M, Kulic A, et al (2011). Prognostic significance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) in patients with primary invasive ductal breast carcinoma - a 7.5-year follow-up study. Tumori, 97, 532-59.
  20. Jeong YJ, Jeong HY, Bong JG, et al (2013). Low methylation levels of the SFRP1 gene are associated with the basal-like subtype of breast cancer. Oncol Rep, [Epub ahead of print].
  21. Jiao Z, Li D (2013). Lack of association between MHTFR Glu429Ala polymorphism and breast cancer susceptibility: a systematic review and meta-analysis of 29 research studies. Tumour Biol, [Epub ahead of print].
  22. Lee JH, Kim Y, Choi JW, Kim YS (2013). Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis. Arch Med Res, 44, 39-45. https://doi.org/10.1016/j.arcmed.2012.12.002
  23. Li H, Beeghly-Fadiel A, Wen W, et al (2013). Gene-environment interactions for breast cancer risk among Chinese women: a report from the Shanghai breast cancer genetics study. Am J Epidemiol, 177, 161-70. https://doi.org/10.1093/aje/kws238
  24. Martin FL (2013). Epigenetic influences in the aetiology of cancers arising from breast and prostate: a hypothesised transgenerational evolution in chromatin accessibility. ISRN Oncol, 2013, 624794.
  25. Martinelli N, Girelli D, Ferraresi P, et al (2007). Increased factor VIII coagulant activity levels in male carriers of the factor V R2 polymorphism. Blood Coagul Fibrinolysis, 18, 125-9. https://doi.org/10.1097/MBC.0b013e328011c06d
  26. Meryet-Figuières M, Resina S, Lavigne C, et al (2007). Inhibition of PAI-1 expression in breast cancer carcinoma cells by siRNA at nanomolar range. Biochimie, 89, 1228-33. https://doi.org/10.1016/j.biochi.2007.03.017
  27. Muzeyyen I (2013). A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk. Mol Biol Rep, 40, 625-37. https://doi.org/10.1007/s11033-012-2101-2
  28. Nomizu T, Matsuzaki M, Katagata N, et al (2012). A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes. Breast Cancer, [Epub ahead of print].
  29. Offersen BV, Alsner J, Ege OK, et al (2008).A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer. Acta Oncol, 47, 618-32. https://doi.org/10.1080/02841860801958295
  30. Ozdemir O, Yenicesu GI, Silan F, et al (2012). Recurrent pregnancy loss and its relation to combined parental thrombophilic gene mutations. Genet Test Mol Biomarkers, 16, 279-86. https://doi.org/10.1089/gtmb.2011.0191
  31. Ozturk A, Balli S, Akar N (2012). Determination of factor V Leiden mutation and R2 polymorphism in cis position. Clin Appl Thromb Hemost, [Epub ahead of print].
  32. Qi X, Ma X, Yang X, et al (2010). Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a metaanalysis from 41 studies with 16,480 cases and 22,388 controls. Breast Cancer Res Treat, 123, 499-06. https://doi.org/10.1007/s10549-010-0773-7
  33. Sangrajrang S, Sato Y, Sakamoto H, et al (2010). Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case-control study in Thai women. Breast Cancer Res Treat, 123, 885-93. https://doi.org/10.1007/s10549-010-0804-4
  34. Sohail A, Kanwal N, Ali M, et al (2013). Effects of glutathione- S-transferase polymorphisms on the risk of breast cancer: A population-based case-control study in Pakistan. Environ Toxicol Pharmacol, 35, 143-53. https://doi.org/10.1016/j.etap.2012.11.014
  35. Tang L, Han X (2013). The urokinase plasminogen activator system in breast cancer invasion and metastasis. Biomed Pharmacother, 67, 179-82. https://doi.org/10.1016/j.biopha.2012.10.003
  36. Valjevac A, Mehic B, Kiseljakovic E, et al (2013). Prevalence of 1691G>A FV mutation in females from Bosnia and Herzegovina - a preliminary report. Bosn J Basic Med Sci, 13, 31-3.
  37. Valjevac A, Mehic B, Kiseljakovic E, et al (2013). Prevalence of 1691G>A FV mutation in females from Bosnia and Herzegovina - a preliminary report. Bosn J Basic Med Sci, 13, 31-3.
  38. Vrba L, Munoz-Rodriguez JL, Stampfer MR, et al (2013). miRNA gene promoters are frequent targets of aberrant DNA methylation in human breast cancer. PLoS One, 8, 54398. https://doi.org/10.1371/journal.pone.0054398
  39. Werner H, Bruchim I (2013). IGF-1 and BRCA1 signalling pathways in familial cancer. Lancet Oncol, 13, 537-44.
  40. Wu XY, Ni J, Xu WJ, et al (2012). Interactions between MTHFR C677T-A1298C variants and folic acid deficiency affect breast cancer risk in a Chinese population. Asian Pac J Cancer Prev, 13, 2199-06. https://doi.org/10.7314/APJCP.2012.13.5.2199
  41. Xu X, Gammon MD, Hernandez-Vargas H, et al (2012). DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study. FASEB J, 26, 2657-66. https://doi.org/10.1096/fj.11-197251
  42. Yagmurdur MC, Atac FB, Tutar NU, et al ( 2008). Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast. Int Surg, 93, 163-8.
  43. Yamazaki T, Nicolaes GA, Sorensen KW, Dahlback B (2002). Molecular basis of quantitative factor V deficiency associated with factor V R2 haplotype. Blood, 100, 2515-21. https://doi.org/10.1182/blood.V100.7.2515
  44. Zaatari GS, Otrock ZK, Sabbagh AS, Mahfouz RA (2006). Prevalence of factor V R2 (H1299R) polymorphism in the Lebanese population. Pathology, 38, 442-4. https://doi.org/10.1080/00313020600922934
  45. Zheng J, Wang J, Sun X, et al (2013). HIC1 modulates prostate cancer progression by epigenetic modification. Clin Cancer Res, [Epub ahead of print].

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