International Journal of Medical Sciences

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16 December 2017

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Int J Med Sci 2013; 10(12):1755-1760. doi:10.7150/ijms.6749

Research Paper

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

Hideaki Omatsu1,2, Akiko Kuwahara1,3, Motohiro Yamamori1,3, Megumi Fujita3, Tatsuya Okuno4, Ikuya Miki4,5, Takao Tamura4, Kohshi Nishiguchi6, Noboru Okamura3, Tsutomu Nakamura7, Takeshi Azuma4, Takeshi Hirano1, Koichiro Ozawa2, Midori Hirai1✉

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.

Abstract

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.

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How to cite this article:
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