Abstract
Objectives
We evaluated whether DNA repair gene polymorphisms had an effect on clinical outcomes in metastatic/recurrent nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based chemotherapy.
Materials and methods
Clinical data of 101 patients with metastatic/recurrent NPC between 2004 and 2011 were reviewed. Five potentially functional polymorphisms (ERCC1 Asn118Asn, ERCC1 C8092A, XPD Lys751Gln, XRCC1 Arg399Gln and XRCC1 Arg280His) were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Results
The ERCC1 C8092A polymorphism was an independent predictor of PFS in Chinese NPC patients treated with cisplatin-based chemotherapy. Compared to the patients carrying the C/C genotype, the patients with the C/A or A/A genotype had an increased risk of disease progression on cisplatin-based chemotherapy (7.9 vs. 9.3 months; HR 1.61; 95 % CI 1.08–2.61; p = 0.047). However, no association between the other polymorphisms, response rate, disease progression and survival was detected in metastatic/recurrent NPC patients.
Conclusion
The ERCC1 C8092A polymorphism might be a useful predictive marker in metastatic/recurrent NPC patients treated with cisplatin-based chemotherapy. However, a large-scale prospective study is warranted to validate our findings.
Similar content being viewed by others
References
Chang ET, Adami HO (2006) The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 15(10):1765–1777
Bensouda Y, Kaikani W, Ahbeddou N, Rahhali R, Jabri M, Mrabti H, Boussen H, Errihani H (2011) Treatment for metastatic nasopharyngeal carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis 128(2):79–85
Faivre S, Chan D, Salinas R, Woynarowska B, Woynarowski JM (2003) DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol 66(2):225–237
Bernig T, Chanock SJ (2006) Challenges of SNP genotyping and genetic variation: its future role in diagnosis and treatment of cancer. Expert Rev Mol Diagn 6(3):319–331
Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21(4):551–555
Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TD, Mark EJ, Wain JC, Christiani DC, Kelsey KT (2000) Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 21(5):965–971
Krivak TC, Darcy KM, Tian C, Armstrong D, Baysal BE, Gallion H, Ambrosone CB, DeLoia JA (2008) Relationship between ERCC1 polymorphisms, disease progression, and survival in the Gynecologic Oncology Group Phase III Trial of intraperitoneal versus intravenous cisplatin and paclitaxel for stage III epithelial ovarian cancer. J Clin Oncol 26(21):3598–3606
Khrunin AV, Moisseev A, Gorbunova V, Limborska S (2010) Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients. Pharmacogenomics J 10(1):54–61
Steffensen KD, Waldstrom M, Jeppesen U, Brandslund I, Jakobsen A (2008) Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer. Int J Gynecol Cancer 18(4):702–710
Viguier J, Boige V, Miquel C, Pocard M, Giraudeau B, Sabourin JC, Ducreux M, Sarasin A, Praz F (2005) ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer. Clin Cancer Res 11(17):6212–6217
Park DJ, Stoehlmacher J, Zhang W, Tsao-Wei DD, Groshen S, Lenz HJ (2001) A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 61(24):8654–8658
Quintela-Fandino M, Hitt R, Medina PP, Gamarra S, Manso L, Cortes-Funes H, Sanchez-Cespedes M (2006) DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy. J Clin Oncol 24(26):4333–4339
Park SY, Hong YC, Kim JH, Kwak SM, Cho JH, Lee HL, Ryu JS (2006) Effect of ERCC1 polymorphisms and the modification by smoking on the survival of non-small cell lung cancer patients. Med Oncol 23(4):489–498
Ren S, Zhou S, Wu F, Zhang L, Li X, Zhang J, Xu J, Lv M, Zhang J, Zhou C (2012) Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy. Lung Cancer 75(1):102–109
Hopkins J, Cescon DW, Tse D, Bradbury P, Xu W, Ma C, Wheatley-Price P, Waldron J, Goldstein D, Meyer F, Bairati I, Liu G (2008) Genetic polymorphisms and head and neck cancer outcomes: a review. Cancer Epidemiol Biomarkers Prev 17(3):490–499
Cheng XD, Lu WG, Ye F, Wan XY, Xie X (2009) The association of XRCC1 gene single nucleotide polymorphisms with response to neoadjuvant chemotherapy in locally advanced cervical carcinoma. J Exp Clin Cancer Res 28:91
Gurubhagavatula S, Liu G, Park S, Zhou W, Su L, Wain JC, Lynch TJ, Neuberg DS, Christiani DC (2004) XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 22(13):2594–2601
Liao WY, Shih JY, Chang GC, Cheng YK, Yang JC, Chen YM, Yu CJ (2012) Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in non-small-cell lung cancer patients treated with gemcitabine/platinum. J Thorac Oncol 7(6):973–981
Reed E (1998) Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev 24(5):331–344
Reed E (2005) ERCC1 and clinical resistance to platinum-based therapy. Clin Cancer Res 11(17):6100–6102
Enzlin JH, Scharer OD (2002) The active site of the DNA repair endonuclease XPF-ERCC1 forms a highly conserved nuclease motif. EMBO J 21(8):2045–2053
Lee HW, Hwang YH, Han JH, Choi JH, Kang SY, Jeong SH, Ann MS, Oh YT, Kim JH, Kim CH, Sheen SS (2010) High expression of excision repair cross-complementation group 1 protein predicts poor outcome in patients with nasopharyngeal cancer. Oral Oncol 46(3):209–213
Huang PY, Li Y, Mai HQ, Luo RZ, Cai YC, Zhang L (2012) Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy. Oral Oncol 48(10):964–968
Takenaka T, Yano T, Kiyohara C, Miura N, Kouso H, Ohba T, Kometani T, Shoji F, Yoshino I, Maehara Y (2010) Effects of excision repair cross-complementation group 1 (ERCC1) single nucleotide polymorphisms on the prognosis of non-small cell lung cancer patients. Lung Cancer 67(1):101–107
Yu JJ, Lee KB, Mu C, Li Q, Abernathy TV, Bostick-Bruton F, Reed E (2000) Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene. Int J Oncol 16(3):555–560
Park D, Stoehlmacher J, Zhang W, Tsao-Wei D, Groshen S, Lenz H-J (2002) ERCC1 polymorphism is associated with differential ERCC1 gene expression. American Association for Cancer Research, San Francisco, CA
Woelfelschneider A, Popanda O, Lilla C, Linseisen J, Mayer C, Celebi O, Debus J, Bartsch H, Chang-Claude J, Schmezer P (2008) A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients. Carcinogenesis 29(9):1758–1764
Yin M, Yan J, Voutsina A, Tibaldi C, Christiani DC, Heist RS, Rosell R, Booton R, Wei Q (2011) No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta-analysis. Lung Cancer 72(3):370–377
Tay MH, Ong YK, Foo KF (2001) The role of salvage chemotherapy in metastatic nasopharyngeal carcinoma (NPC). Proc Am Soc Clin Oncol 20 (abstract2547)
Ma BB, Hui EP, Wong SC, Tung SY, Yuen KK, King A, Chan SL, Leung SF, Kam MK, Yu BK, Zee B, Chan AT (2009) Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma—correlation with excision repair cross-complementing-1 polymorphisms. Ann Oncol 20(11):1854–1859
Acknowledgments
This work was supported by grants from the National “863” science and technology support program of China (No. 2003A3080202), the National Natural Science Foundation of China (No. 81172565) and the medical scientific research fund project of Guangdong province (No. WSTTJJ20071127).
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
Cui Chen and Fenghua Wang have equally contributed to this work.
Rights and permissions
About this article
Cite this article
Chen, C., Wang, F., Wang, Z. et al. Polymorphisms in ERCC1 C8092A predict progression-free survival in metastatic/recurrent nasopharyngeal carcinoma treated with cisplatin-based chemotherapy. Cancer Chemother Pharmacol 72, 315–322 (2013). https://doi.org/10.1007/s00280-013-2196-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-013-2196-8