Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan–Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8−35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6−75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0−127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6−88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.
Non-small cell lung cancer Gene polymorphisms XRCC1 ERCC1 XPD p53
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The study was approved by the Ethical Board of the Meram Medical School of Selcuk University and performed with the financial support of the Scientific Research Project of Selcuk University (Project no: 11102028) in Konya, Turkey.
Mathiaux J, Le Morvan V, Pulido M, Jougon J, Bégueret H, Robert J. Role of DNA repair gene polymorphisms in the efficiency of platinum-based adjuvant chemotherapy for non-small cell lung cancer. Mol Diagn Ther. 2011;15(3):159–66.CrossRefPubMedGoogle Scholar
Yin M, Yan J, Voutsina A, Tibaldi C, Christiani DC, Heist RS, et al. 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. 2011;72(3):370–7.CrossRefPubMedGoogle Scholar
Ma H, Xu L, Yuan J, Shao M, Hu Z, Wang F, et al. Tagging single nucleotide polymorphisms in excision repair cross-complementing group 1 (ERCC1) and risk of primary lung cancer in a Chinese population. Pharmacogenet Genomics. 2007;17(6):417–23.CrossRefPubMedGoogle Scholar
Kim M, Kang HG, Lee SY, Lee HC, Lee EB, Choi YY, et al. Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer. Cancer Sci. 2010;101(11):2436–42.CrossRefPubMedGoogle Scholar
Reed E. Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev. 1998;24(5):331–44.CrossRefPubMedGoogle Scholar
Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, et al. XPD polymorphisms: effects on DNA repair capacity. Carcinogenesis. 2000;21(4):551–5.CrossRefPubMedGoogle Scholar
Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S. Human xeroderma pigmentosum group D geneencodes a DNA helicase. Nature. 1993;365(6449):852–5.CrossRefPubMedGoogle Scholar
Wei SZ, Zhan P, Shi MQ, Shi Y, Qian Q, Yu LK, et al. Predictive value of ERCC1 and XPD polymorphism in patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a systematic review and meta-analysis. Med Oncol. 2011;28(1):315–21.CrossRefPubMedGoogle Scholar
Vilmar A, Sørensen JB. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer. 2009;64(2):131–9.CrossRefPubMedGoogle Scholar
Giachino DF, Ghio P, Regazzoni S, Mandrile G, Novello S, Selvaggi G, et al. Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer. Clin Cancer Res. 2007;13(10):2876–81.CrossRefPubMedGoogle Scholar
Gurubhagavatula S, Liu G, Park S, Zhou W, Su L, Wain JC, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol. 2004;22(13):2594–601.CrossRefPubMedGoogle Scholar
Gandara DR, Kawaguchi T, Crowley J, Moon J, Furuse K, Kawahara M, et al. Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics. J Clin Oncol. 2009;27(21):3540–6.CrossRefPubMedPubMedCentralGoogle Scholar
de las Peñas R, Sanchez-Ronco M, Alberola V, Taron M, Camps C, Garcia-Carbonero R, et al. Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients. Ann Oncol. 2006;17(4):668–75.CrossRefPubMedGoogle Scholar
Yao CY, Huang XE, Li C, Shen HB, Shi MQ, Feng JF, et al. Lack of influence of XRCC1 and XPD gene polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancers. Asian Pac J Cancer Prev. 2009;10(5):859–64.PubMedGoogle Scholar
Shiraishi K, Kohno T, Tanai C, Goto Y, Kuchiba A, Yamamoto S, et al. Association of DNA repair gene polymorphisms with response to platinum-based doublet chemotherapy in patients with non-small-cell lung cancer. J Clin Oncol. 2010;28(33):4945–52.CrossRefPubMedGoogle Scholar
Isla D, Sarries C, Rosell R, Alonso G, Domine M, Taron M, et al. Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol. 2004;15(8):1194–203.CrossRefPubMedGoogle Scholar
Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355(10):983–91.CrossRefPubMedGoogle Scholar
Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8(7):2286–91.PubMedGoogle Scholar
Tibaldi C, Giovannetti E, Vasile E, Mey V, Laan AC, Nannizzi S, et al. Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res. 2008;14(6):1797–803.CrossRefPubMedGoogle Scholar