DOI QR코드

DOI QR Code

The Role of Genetic Polymorphisms in Nrf2 and P73 in Egyptian Women with Breast Cancer

  • Azhary, Nevin M Al (Biochemistry and Molecular Medicine Department, College of Medicine, Taibah University) ;
  • Kamel, Mahmoud M (Department of Clinical Pathology, National Cancer Institute, Cairo University) ;
  • Ismail, Yahia M (Department of Medical Oncology, National Cancer Institute, Cairo University) ;
  • Mahmoud, Amal A (Clinical Pathology Department, Faculty of Medicine, Assiut University) ;
  • Radwan, Enas M (Department of Clinical Pathology, National Cancer Institute, Cairo University)
  • Published : 2016.11.01

Abstract

Background: Breast cancer is the commonest cancer in Egyptian females. Nrf2 is involved in oxidative stress while P73 functions in response to DNA damage. This study aimed to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 SNPs in breast cancer in Egypt. Patients: Eighty-five female patients with breast tumours (41 malignant, 44 benign) were included. Nrf2 (rs6721961) and p73 (G4A) SNPs were determined by PCR- CTPP assay. Results: Genotype frequencies of the Nrf2 promoter SNP were 34.2% and 37.9% for AA in benign and malignant groups respectively, and 43.9% and 40.5% for CC and, 21.9 % and 21.6% for CA. Genotype frequencies for the P73 G4A SNP were 52.9% and 44.7% for GA in benign and malignant groups respectively, and 47.1% and 55.3% for GG. Discussion: Nrf2 genotypes in pre - and post-menopausal patients, showed significantly different distributions in the 2 patient groups, the AA genotype being significantly more common in pre-menopausal patients. The P73 G4A SNP showed no relation to age of disease onset. Conclusion: The Nrf2 (rs6721961) AA genotype might be related to early breast cancer onset. In contrast the P73 G4A polymorphism showed no relation to either disease risk or age at presentation.

Keywords

Breast cancer;polymorphisms;Nrf2;P73;genotype

References

  1. Chen J, Li D, Killary A, et al (2008). Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. Ann SurgOncol, 16, 431-39.
  2. Cutruzzola F, Avigliano L, Candi E (2013). p73 keeps metabolic control in balance. Cell Cycle, 13, 179-80.
  3. Dotsch V, Bernassola F, Coutandin D, et al (2010). p63 and p73, the Ancestors of p53. Cold Spring Harb Perspect Biol, 2, a004887-a004887.
  4. El Saghir N, Khalil M, Eid T, et al (2007). Trends in epidemiology and management of breast cancer in developing Arab countries: A literature and registry analysis. Int J Surg, 5, 225-33. https://doi.org/10.1016/j.ijsu.2006.06.015
  5. El Saghir N, Seoud M, Khalil M, et al (2006). Effects of young age at presentation on survival in breast cancer. BMC Cancer, 6,194. https://doi.org/10.1186/1471-2407-6-194
  6. Fang Y, Chen Y, Yu L, et al (2012). Inhibition of breast cancer metastases by a novel inhibitor of TGF Receptor 1. JNCI J. Natl Cancer Inst, 105, 47-58.
  7. Ferlay J, Shin H, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-2917. https://doi.org/10.1002/ijc.25516
  8. Furfaro A, Traverso N, Domenicotti C, et al (2016). The Nrf2/ HO-1 axis in cancer cell growth and chemoresistance. Oxid Med Cell Longev, 2016, 1-14.
  9. Galli P, Cadoni G, Volante M, et al (2009). A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population. BMC Cancer, 9, 137. https://doi.org/10.1186/1471-2407-9-137
  10. Gomes L, Terra L, Wailemann R, et al (2012). TGF-${\beta}1$ modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells. BMC Cancer, 12, 26. https://doi.org/10.1186/1471-2407-12-26
  11. Hamajima N, Saito T, Matsuo K, et al (2000). Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Jpn J Cancer Res, 91, 865-68. https://doi.org/10.1111/j.1349-7006.2000.tb01026.x
  12. Hartikainen J, Tengstrom M, Kosma V, et al (2012). Genetic polymorphisms and protein expression of NRF2 and sulfiredoxin predict survival outcomes in breast cancer. Cancer Res, 72, 5537-46. https://doi.org/10.1158/0008-5472.CAN-12-1474
  13. Ibrahim A, Khaled H, Mikhail N, et al (2014). Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program. J Cancer Epidemiol, 2014, 1-18.
  14. Inoue D, Suzuki T, Mitsuishi Y, et al (2012). Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Science, 103, 760-66. https://doi.org/10.1111/j.1349-7006.2012.02216.x
  15. Inoue S, Tomasini R, Rufini A, et al (2014). TAp73 is required for spermatogenesis and the maintenance of male fertility. Proc Natl Acad Sci USA, 111, 1843-48. https://doi.org/10.1073/pnas.1323416111
  16. Ishikawa T, (2014). Personalized medicine research institute, NGO personalized medicine and healthcare, Yokohama, Japan RIKEN center for life science technologies, Yokohama, Japan: Mini Review Article.
  17. Jaramillo M, Zhang D (2013). The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev, 27, 2179-91. https://doi.org/10.1101/gad.225680.113
  18. Jeong W, Jun M, Kong A (2006). Nrf2: A potential molecular target for cancer chemoprevention by natural compounds. Antioxid Redox Signal, 8, 99-106. https://doi.org/10.1089/ars.2006.8.99
  19. Kensler T, Wakabayashi N, Biswal S (2007). Cell survival responses to environmental stresses via the keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol, 47, 89-116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046
  20. Konstantinopoulos P, Spentzos D, Fountzilas E, et al (2011). Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res, 71, 5081-89. https://doi.org/10.1158/0008-5472.CAN-10-4668
  21. Lau A, Villeneuve N, Sun Z, et al (2008). Dual roles of Nrf2 in cancer. Pharmacol Res, 58, 262-70. https://doi.org/10.1016/j.phrs.2008.09.003
  22. Lee K (2010). p73 G4C14 to A4T14 polymorphism is associated with colorectal cancer risk and survival. World J Gastroenterol, 16, 4448. https://doi.org/10.3748/wjg.v16.i35.4448
  23. Li H, Yao L, Ouyang T, et al (2006). Association of p73 G4C14-to-A4T14 (GC/AT) polymorphism with breast cancer survival. Carcinogenesis, 28, 372-77. https://doi.org/10.1093/carcin/bgl153
  24. Liu Y, Dong W, Mou Q, et al (2014). Impact of p73 gene polymorphism on cancer susceptibility: a meta-analysis. Int J Clin Exp Pathol, 7, 6820-25.
  25. Manandhar S, Choi B, Jung K, et al (2012). NRF2 inhibition represses ErbB2 signaling in ovarian carcinoma cells: Implications for tumor growth retardation and docetaxel sensitivity. Free Radic Biol Med, 52, 1773-85. https://doi.org/10.1016/j.freeradbiomed.2012.02.031
  26. Marzec J, Christie J, Reddy S, et al (2007). Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J, 21, 2237-46. https://doi.org/10.1096/fj.06-7759com
  27. Mitsuishi Y, Motohashi H, Yamamoto M (2012). The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Front Oncol, 2, 135.
  28. Motohashi H, Yamamoto M (2004). Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med, 10, 549-57. https://doi.org/10.1016/j.molmed.2004.09.003
  29. Onodera Y, Motohashi H, Takagi K, et al (2013). NRF2 immunolocalization in human breast cancer patients as a prognostic factor. Endocr Relat Cancer, 21, 241-52.
  30. Pal S, Childs B, Pegram M (2010). Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat, 125, 627-36.
  31. Porter P (2009). Global trends in breast cancer incidence and mortality. Salud Publica Mex, 51, 141-46. https://doi.org/10.1590/S0036-36342009000800003
  32. Shimoyama Y, Mitsuda Y, Tsuruta Y, et al (2014). Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure and cardiovascular mortality in hemodialysis patients. Nagoya J Med Sci, 11, 726-31.
  33. Solis L, Behrens C, Dong W, et al (2010). Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res, 16, 3743-53. https://doi.org/10.1158/1078-0432.CCR-09-3352
  34. von Minckwitz G, Untch M, Nuesch E, et al (2010). Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat, 125, 145-56.
  35. Wang J, Zhang M, Zhang L, Cai H, et al (2010). Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res, 164, 99-105. https://doi.org/10.1016/j.jss.2010.05.058
  36. Wang L, Gao R, Yu L (2011). Combined analysis of the association between p73 G4C14-to-A4T14 polymorphisms and cancer risk. Mol Biol Rep, 39, 1731-38.
  37. Wang X, Sun Z, Villeneuve N, et al (2008). Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis, 29, 1235-43. https://doi.org/10.1093/carcin/bgn095
  38. Zhang D (2006). Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev, 38, 769-89. https://doi.org/10.1080/03602530600971974
  39. Zhou X, Wu C (2012). Association of p73 G4C14-A4T14 polymorphisms with genetic susceptibilities to breast cancer: a case-control study. Med Oncol, 29, 3216-21. https://doi.org/10.1007/s12032-012-0240-x