International Journal of Medical Sciences

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13 December 2017

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Int J Med Sci 2014; 11(4):321-326. doi:10.7150/ijms.7654

Research Paper

Genetic Polymorphisms in SLC23A2 as Predictive Biomarkers of Severe Acute Toxicities after Treatment with a Definitive 5-Fluorouracil/Cisplatin-Based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma

Tetsuya Minegaki1, Akiko Kuwahara2,3, Motohiro Yamamori2,3, Tsutomu Nakamura2, Tatsuya Okuno2, Ikuya Miki2, Hideaki Omatsu2, Takao Tamura2,4, Midori Hirai2, Takeshi Azuma2, Toshiyuki Sakaeda2,5✉, Kohshi Nishiguchi1,2✉

1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
3. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
4. Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Nara 630-0293, Japan.
5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.

Abstract

Objective: Definitive chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) is one of the standard therapies for esophageal squamous cell carcinoma (ESCC); however, inter-individual variations in clinical outcomes have yet to be investigated. In the present study, single nucleotide polymorphisms (SNPs) in SLC23A2 gene were retrospectively evaluated in 49 Japanese patients with ESCC who were treated with a definitive 5-FU/CDDP-based CRT, and the predictive values for the clinical response, severe acute toxicities, and long-term survival were assessed.

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 to 5, 8 to 12, and 15 to 19, with a second course being repeated after a 2-week interval. The SLC23A2 SNPs rs2681116, rs13037458, rs1715364, rs4987219, and rs1110277 were evaluated.

Results: The rs2681116 and rs13037458 had a tendency to predict the clinical response (p=0.144 and 0.085, respectively) and long-term survival (p=0.142 and 0.056, respectively). The rs4987219 and rs1110277 correlated with severe acute leukopenia (p=0.025) and stomatitis (p=0.019), respectively.

Conclusions: Further investigations with a larger number of patients or an in vitro study are needed to confirm the predictive values of genetic polymorphisms in SLC23A2.

Keywords: esophageal squamous cell carcinoma, chemoradiotherapy, biomarker, SLC23A2, polymorphism.

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How to cite this article:
Minegaki T, Kuwahara A, Yamamori M, Nakamura T, Okuno T, Miki I, Omatsu H, Tamura T, Hirai M, Azuma T, Sakaeda T, Nishiguchi K. Genetic Polymorphisms in SLC23A2 as Predictive Biomarkers of Severe Acute Toxicities after Treatment with a Definitive 5-Fluorouracil/Cisplatin-Based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma. Int J Med Sci 2014; 11(4):321-326. doi:10.7150/ijms.7654. Available from http://www.medsci.org/v11p0321.htm