DOI QR코드

DOI QR Code

Single Nucleotide Polymorphisms in the NER Pathway and Clinical Outcome of Patients with Bone Malignant Tumor

  • Sun, Xiao-Hui (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University) ;
  • Hou, Wen-Gen (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University) ;
  • Zhao, Hong-Xing (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University) ;
  • Zhao, Yi-Lei (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University) ;
  • Ma, Chao (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University) ;
  • Liu, Ying (Department of Orthopaedics, the First Affiliated Hospital of Xinxiang Medical University)
  • Published : 2013.03.30

Abstract

The effects of polymorphisms in ERCC5, ERCC6, XPC, CCNH and MMS19L on osteosarcoma response to chemotherapy and the survival of the affected patients were assessed. Genotyping of ERCC5, ERCC6, XPC, CCNH and MMS19L was performed by PCR-RFLP assay. The median PFS was 12.8 months, and the median OS was 18.6 months. Individuals carrying homozygous genotypes of ERCC5 rs17655 and ERCC5 rs1047768 were more like to have good response to treatment, while those carrying homozygous genotypes of MMS19L rs29001322 showed poor response. Osteosarcoma patients carrying TT genotype of ERCC5 rs1047768 showed a significantly longer PFS (16.8 months) and OS (21.4 months) than CC genotype, with HRs(95% CI) of 0.31 (0.10-0.93) and 0.32 (0.06-0.97), respectively. Conversely, those with the TT genotype of MMS19L rs29001322 demonstrated shorter PFS and OS, the HRs (95% CI) being 2.23 (1.08-4.15) and 4.62 (1.45-16.08), respectively. Our findings showed polymorphisms in ERCC5 rs1047768 and MMS19L rs29001322 to be associated with clinical outcome of osteosarcoma patients undergoing chemotherapy.

Acknowledgement

Supported by : Education Department of Henan Province

References

  1. Biason P, Hattinger CM, Innocenti F, et al (2012). Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. Pharmacogenomics J, 12, 476-83. https://doi.org/10.1038/tpj.2011.33
  2. Caronia D, Patiño-García A, Milne RL, et al (2009). Common variations in ERCC2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients. Pharmacogenomics J, 9, 347-53. https://doi.org/10.1038/tpj.2009.19
  3. Chou AJ, Gorlick R (2006) Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther, 6, 1075-85. https://doi.org/10.1586/14737140.6.7.1075
  4. Dogan M, Karabulut HG, Tukun A, et al (2012). Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients. Asian Pac J Cancer Prev, 13, 1553-6. https://doi.org/10.7314/APJCP.2012.13.4.1553
  5. Goode EL, Ulrich CM, Potter JD (2002). Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev, 11, 1513-30.
  6. Le MV, Longy M, Bonaiti-Pellie C, et al (2006). Genetic polymorphisms of the XPG and XPD nucleotide excision repair genes in sarcoma patients. Int J Cancer, 119, 1732-5. https://doi.org/10.1002/ijc.22009
  7. Hatfield MD, Reis AM, Obeso D, et al (2006). Identification of MMS19 domains with distinct functions in NER and transcription. DNA Repair (Amst), 5, 914-24. https://doi.org/10.1016/j.dnarep.2006.05.007
  8. Hattinger CM, Pasello M, Ferrari S, et al (2010). Emerging drugs for high-grade osteosarcoma. Expert Opin Emerg Drugs, 15, 615-34. https://doi.org/10.1517/14728214.2010.505603
  9. Koeppel F, Poindessous V, Lazar V, et al (2004). Irofulven cytotoxicity depends on transcription-coupled nucleotide excision repair and is correlated with XPG expression in solid tumor cells. Clin Cancer Res, 10, 5604-13. https://doi.org/10.1158/1078-0432.CCR-04-0442
  10. Liu D, Wu HZ, Zhang YN, et al (2012). DNA repair genes XPC, XPG polymorphisms: relation to the risk of colorectal carcinoma and therapeutic outcome with Oxaliplatin-based adjuvant chemotherapy. Mol Carcinog, 51, E83-93. https://doi.org/10.1002/mc.21862
  11. Martin LP, Hamilton TC, Schilder RJ (2008). Platinum resistance: the role of DNA repair pathways. Clin Cancer Res, 14, 1291-5. https://doi.org/10.1158/1078-0432.CCR-07-2238
  12. Massuti B, Cobo M, Camps C, et al (2012). Trabectedin in patients with advanced non-small-cell lung cancer (NSCLC) with XPG and/or ERCC1 overexpression and BRCA1 underexpression and pretreated with platinum. Lung Cancer, 76, 354-61. https://doi.org/10.1016/j.lungcan.2011.12.002
  13. McWilliams RR, Bamlet WR, de Andrade M, et al (2009). Nucleotide excision repair pathway polymorphisms and pancreatic cancer risk: evidence for role of MMS19L. Cancer Epidemiol Biomarkers Prev, 18, 1295-302. https://doi.org/10.1158/1055-9965.EPI-08-1109
  14. Ott K, Rachakonda PS, Panzram B, et al (2011). DNA repair gene and MTHFR gene polymorphisms as prognostic markers in locally advanced adenocarcinoma of the esophagus or stomach treated with cisplatin and 5-fluorouracil-based neoadjuvant chemotherapy. Ann Surg Oncol, 18, 2688-98. https://doi.org/10.1245/s10434-011-1601-y
  15. Reed E (1998). Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev, 24, 331-44. https://doi.org/10.1016/S0305-7372(98)90056-1
  16. Schöffski P, Taron M, Jimeno J, et al (2011). Predictive impact of DNA repair functionality on clinical outcome of advanced sarcoma patients treated with trabectedin: a retrospective multicentric study. Eur J Cancer, 47, 1006-12. https://doi.org/10.1016/j.ejca.2011.01.016
  17. Stoehlmacher J, Park DJ, Zhang W, et al (2004). A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer, 91, 344-54.
  18. Zhang L, Gao G, Li X, et al (2012). Association between single nucleotide polymorphisms (SNPs) and toxicity of advanced non-small-cell lung cancer patients treated with chemotherapy. PLoS One, 7, e48350. https://doi.org/10.1371/journal.pone.0048350
  19. Zhou SF, Di YM, Chan E, et al (2008) Clinical pharmacogenetics and potential application in personalized medicine. Curr Drug Metab, 9, 738-84. https://doi.org/10.2174/138920008786049302

Cited by

  1. Role of DNA Repair-related Gene Polymorphisms in Susceptibility to Risk of Prostate Cancer vol.14, pp.10, 2013, https://doi.org/10.7314/APJCP.2013.14.10.5839
  2. Extraskeletal Ewing Sarcomas in Late Adolescence and Adults: A Study of 37 Patients vol.14, pp.5, 2013, https://doi.org/10.7314/APJCP.2013.14.5.2967
  3. ERCC polymorphisms and prognosis of patients with osteosarcoma vol.35, pp.10, 2014, https://doi.org/10.1007/s13277-014-2322-1
  4. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? vol.5, pp.1664-8021, 2014, https://doi.org/10.3389/fgene.2014.00391
  5. The pharmacogenomics of osteosarcoma vol.17, pp.1, 2017, https://doi.org/10.1038/tpj.2016.45