Int J Med Sci 2013; 10(12):1755-1760. doi:10.7150/ijms.6749
TNF-α -857C>T Genotype is Predictive of Clinical Response after Treatment with Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma
1. Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe 650-0017, Japan;
2. Department of Pharmacotherapy, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan;
3. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan;
4. Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan;
5. Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;
6. Department of Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;
7. Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan.
Omatsu H, Kuwahara A, Yamamori M, Fujita M, Okuno T, Miki I, Tamura T, Nishiguchi K, Okamura N, Nakamura T, Azuma T, Hirano T, Ozawa K, Hirai M. TNF-α -857C>T Genotype is Predictive of Clinical Response after Treatment with Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma. Int J Med Sci 2013; 10(12):1755-1760. doi:10.7150/ijms.6749. Available from http://www.medsci.org/v10p1755.htm
Background: Genotypes of tumor necrosis factor alpha (TNF-α) and its surface receptors, TNFRSF1A and TNFRSF1B, have been examined in terms of the progression, metastasis, clinical efficacy, and prognosis of various cancers; however, little is known about their effects on clinical outcome in patients with esophageal squamous cell carcinoma (ESCC). In this study, TNF-α and TNFRSF1A genotypes were retrospectively evaluated in terms of predicting clinical response, long-term survival, and severe acute toxicities in 46 male Japanese ESCC patients treated with definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT).
Methods: A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course being repeated after a 2-week interval. The TNF-α -1031T>C (rs1799964), -863C>A (rs1800630), -857C>T (rs1799724), -308G>A (rs1800629), -238G>A (rs361525), TNFRSF1A -609G>T (rs4149570), and 36A>G (rs767455) genotypes were evaluated.
Results: The TNF-α -857C>T genotype was found to be predictive of clinical response, i.e., complete response or not (P = 0.010, Fisher's exact test), but had no effect on long-term survival (CC-857 vs. CT-857 + TT-857, P = 0.072, Fisher's exact test, P = 0.070, Log-rank test).
Conclusions: The TNF-α -857C>T genotype was found to be predictive of clinical response and was more likely to predict long-term survival in Japanese ESCC patients receiving definitive 5-FU/CDDP-based CRT. Further clinical investigations with a larger number of patients or experiments in vitro should be performed to assess the predictive value of this genotype following CRT.
Keywords: esophageal squamous cell carcinoma, chemoradiotherapy, clinical response, prognosis, tumor necrosis factor.