Abstract
The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-β1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-β1 C-509T and T+869C. Kaplan–Meier survival analysis, log-rank test, and Cox’s proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-β1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-β1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-β1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.
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References
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Stinchcombe TE, Bogart JA. Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer. Oncologist. 2012;17:682–93.
Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.
Finkelstein DM, Ettinger DS, Ruckdeschel JC. Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1986;4:702–9.
Bi N, Yang M, Zhang L, et al. Cyclooxygenase-2 genetic variants are associated with survival in unresectable locally advanced non-small cell lung cancer. Clin Cancer Res. 2010;16:2383–90.
Guan X, Liao Z, Ma H, et al. TNFRSF1B +676 T>G polymorphism predicts survival of non-small cell lung cancer patients treated with chemoradiotherapy. BMC Cancer. 2011;11:447.
Grainger DJ, Heathcote K, Chiano M, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8:93–7.
Dunning AM, Ellis PD, McBride S, et al. A transforming growth factor beta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res. 2003;63:2610–5.
Guerra JL, Gomez D, Wei Q, et al. Association between single nucleotide polymorphisms of the transforming growth factor β1 gene and the risk of severe radiation esophagitis in patients with lung cancer. Radiother Oncol. 2012;104:365–9.
Minamiya Y, Miura M, Hinai Y, et al. Transforming growth factor-β1 29T>C genetic polymorphism is associated with lymph node metastasis in patients with adenocarcinoma of the lung. Tumour Biol. 2010;31:437–41.
Kelsey CR, Jackson L, Langdon S, et al. A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint. Int J Radiat Oncol Biol Phys. 2012;82:e247–55.
Togashi Y, Masago K, Fujita S, et al. Association of the transforming growth factor β1 promoter polymorphism, C-509T, with smoking status and survival in advanced non-small cell lung cancer. Oncol Rep. 2011;25:377–82.
Lin M, Stewart DJ, Spitz MR, et al. Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer. Carcinogenesis. 2011;32:1050–6.
Zhao L, Ji W, Zhang L, et al. Changes of circulating transforming growth factor-beta1 level during radiation therapy are correlated with the prognosis of locally advanced non-small cell lung cancer. J Thorac Oncol. 2010;5:521–5.
Fu XL, Huang H, Bentel G, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V(30) and transforming growth factor beta. Int J Radiat Oncol Biol Phys. 2001;50:899–908.
Zhao L, Wang L, Ji W, et al. Elevation of plasma TGF-beta1 during radiation therapy predicts radiation-induced lung toxicity in patients with non-small-cell lung cancer: a combined analysis from Beijing and Michigan. Int J Radiat Oncol Biol Phys. 2009;74:1385–90.
Sterlacci W, Wolf D, Savic S, et al. High transforming growth factor β expression represents an important prognostic parameter for surgically resected non-small cell lung cancer. Hum Pathol. 2012;43:339–49.
Heldin CH, Vanlandewijck M, Moustakas A. Regulation of EMT by TGFβ in cancer. FEBS Lett. 2012;586:1959–70.
Shintani Y, Okimura A, Sato K, et al. Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer. Ann Thorac Surg. 2011;92:1794–804.
Soltermann A, Tischler V, Arbogast S, et al. Prognostic significance of epithelial–mesenchymal and mesenchymal–epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res. 2008;14:7430–7.
Acknowledgments
This research was supported by Wenzhou Science and Technology Bureau of China (Grants No. 2011S0057). We thank Dr. Jing Zhao for her assistance in genotyping and statistical analysis of the data.
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The authors declare that they have no competing interests.
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Xue, SL., Zheng, YH., Su, HF. et al. Association between single nucleotide polymorphisms of the transforming growth factor-beta1 gene and overall survival in unresectable locally advanced non-small-cell lung cancer patients treated with radio(chemo)therapy in a Chinese population. Med Oncol 30, 512 (2013). https://doi.org/10.1007/s12032-013-0512-0
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DOI: https://doi.org/10.1007/s12032-013-0512-0