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.

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/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/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.

• Authors: Hideaki Omatsu, Akiko Kuwahara, Motohiro Yamamori, Megumi Fujita, Tatsuya Okuno, Ikuya Miki, Takao Tamura, Kohshi Nishiguchi, Noboru Okamura, Tsutomu Nakamura, Takeshi Azuma, Takeshi Hirano, Koichiro Ozawa, Midori Hirai
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 10 Issue 12 Pg. 1755-60 ( 2013) ISSN: 1449-1907 [Electronic] Australia
• PMID: 24151445 (Publication Type: Journal Article)

Chemical References

• Tumor Necrosis Factor-alpha
• Cisplatin
• Fluorouracil

Topics

• Aged
• Carcinoma, Squamous Cell (genetics, pathology)
• Cisplatin (administration & dosage, adverse effects)
• Combined Modality Therapy
• Drug-Related Side Effects and Adverse Reactions (genetics)
• Esophageal Neoplasms (genetics, pathology)
• Esophageal Squamous Cell Carcinoma
• Fluorouracil (administration & dosage, adverse effects)
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis
• Retrospective Studies
• Survival Analysis
• Treatment Outcome
• Tumor Necrosis Factor-alpha (genetics)