Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Association of NRF2 Polymorphism with Cholangiocarcinoma Prognosis in Thai Patients

  • Published : 2014.01.15
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Abstract

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

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References

  1. Bouligand J, Cabaret O, Canonico M, et al (2011). Effect of NFE2L2 genetic polymorphism on the association between oral estrogen therapy and the risk of venous thromboembolism in postmenopausal women. Clin Pharmacol Ther, 89, 60-4. https://doi.org/10.1038/clpt.2010.241
  2. Buranrat B, Chau-In S, Prawan A, et al (2012). NQO1 expression correlates with cholangiocarcinoma prognosis. Asian Pac J Cancer Prev, 13, 131-6. https://doi.org/10.7314/APJCP.2012.13.1.131
  3. Cardinale V, Semeraro R, Torrice A, et al (2010). Intra-hepatic and extra-hepatic cholangiocarcinoma: New insight into epidemiology and risk factors. World J Gastrointest Oncol, 2, 407-16. https://doi.org/10.4251/wjgo.v2.i11.407
  4. Cordova EJ, Velazquez-Cruz R, Centeno F, et al (2010). The NRF2 gene variant,-653G/A, is associated with nephritis in childhood-onset systemic lupus erythematosus. Lupus, 19, 1237-42. https://doi.org/10.1177/0961203310367917
  5. Guglielmi A, Ruzzenente A, Campagnaro T, et al (2009). Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg, 33, 1247-54. https://doi.org/10.1007/s00268-009-9970-0
  6. Hartikainen JM, Tengstrom M, Kosma VM, 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
  7. Hong CC, Ambrosone CB, Ahn J, et al (2007). Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev, 16, 1784-94. https://doi.org/10.1158/1055-9965.EPI-07-0247
  8. Honjo S, Srivatanakul P, Sriplung H, et al (2005). Genetic and environmental determinants of risk for cholangiocarcinoma via Opisthorchis viverrini in a densely infested area in Nakhon Phanom, northeast Thailand. Int J Cancer, 117, 854-60. https://doi.org/10.1002/ijc.21146
  9. Khan SA, Toledano MB, Taylor-Robinson SD (2008). Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB, 10, 77-82. https://doi.org/10.1080/13651820801992641
  10. Kukongviriyapan V (2012). Genetic polymorphism of drug metabolizing enzymes in association with risk of bile duct cancer. Asian Pac J Cancer Prev, 13, 7-15.
  11. Ma X, Zhang J, Liu S, et al (2012). Nrf2 knockdown by shRNA inhibits tumor growth and increases efficacy of chemotherapy in cervical cancer. Cancer Chemother Pharmacol, 69, 485-94. https://doi.org/10.1007/s00280-011-1722-9
  12. Manandhar S, Choi BH, Jung KA, 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
  13. Marczak ED, Marzec J, Zeldin DC, et al (2012). Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. Pharmacogenet Genomics, 22, 620-8. https://doi.org/10.1097/FPC.0b013e32835516e5
  14. Marzec JM, Christie JD, Reddy SP, 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
  15. Masuko H, Sakamoto T, Kaneko Y, et al (2011). An interaction between Nrf2 polymorphisms and smoking status affects annual decline in FEV1: a longitudinal retrospective cohort study. BMC Med Genet, 12, 97.
  16. Ohshima H, Bandaletova TY, Brouet I, et al (1994). Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase induced in hamsters infected with liver fluke (Opisthorchis viverrini). Carcinogenesis, 15, 271-5. https://doi.org/10.1093/carcin/15.2.271
  17. Okano Y, Nezu U, Enokida Y, et al (2013). SNP (-617C>A) in ARE-Like Loci of the NRF2 Gene: A New Biomarker for Prognosis of Lung Adenocarcinoma in Japanese Non-Smoking Women. PLoS One, 8, 73794. https://doi.org/10.1371/journal.pone.0073794
  18. Prawan A, Kukongviriyapan V, Tassaneeyakul W, et al (2005). Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma. Eur J Cancer Prev, 14, 245-50. https://doi.org/10.1097/00008469-200506000-00008
  19. Ren D, Villeneuve NF, Jiang T, et al (2011). Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Proc Natl Acad Sci USA, 108, 1433-8. https://doi.org/10.1073/pnas.1014275108
  20. Rushmore TH, Morton MRPickett CB (1991). The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem, 266, 11632-9.
  21. Siedlinski M, Postma DS, Boer JM, et al (2009). Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population. Respir Res, 10, 73. https://doi.org/10.1186/1465-9921-10-73
  22. Singal AK, Vauthey JN, Grady JJStroehlein JR (2011). Intrahepatic cholangiocarcinoma--frequency and demographic patterns: thirty-year data from the M.D. Anderson Cancer Center. J Cancer Res Clin Oncol, 137, 1071-8. https://doi.org/10.1007/s00432-010-0971-z
  23. Srivatanakul P, Ohshima H, Khlat M, et al (1991). Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer, 48, 821-5. https://doi.org/10.1002/ijc.2910480606
  24. Subimerb C, Pinlaor S, Khuntikeo N, et al (2010). Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma. Mol Med Rep, 3, 597-605.
  25. Taguchi K, Motohashi HYamamoto M (2011). Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells, 16, 123-40. https://doi.org/10.1111/j.1365-2443.2010.01473.x
  26. Venugopal RJaiswal AK (1996). Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc Natl Acad Sci USA, 93, 14960-5. https://doi.org/10.1073/pnas.93.25.14960
  27. von Otter M, Landgren S, Nilsson S, et al (2010). Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease. BMC Med Genet, 11, 36.
  28. Wirasorn K, Ngamprasertchai T, Chindaprasirt J, et al (2013). Prognostic factors in resectable cholangiocarcinoma patients: Carcinoembryonic antigen, lymph node, surgical margin and chemotherapy. World J Gastrointest Oncol, 5, 81-7. https://doi.org/10.4253/wjge.v5.i3.81

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