Int J Med Sci 2012; 9(9):748-756. doi:10.7150/ijms.5081

Research Paper

THRB Genetic Polymorphisms Can Predict Severe Myelotoxicity after Definitive Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma

Ikuya Miki1,2, Tsutomu Nakamura3,4, Akiko Kuwahara3,5, Motohiro Yamamori3,5, Kohshi Nishiguchi3,6, Takao Tamura1, Tatsuya Okuno1, Hideaki Omatsu3, Shigeto Mizuno2, Midori Hirai3, Takeshi Azuma1, Toshiyuki Sakaeda3,7✉

1. Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan;
2. Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan;
3. Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe 650-0017, Japan;
4. Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan;
5. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan;
6. Department of Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;
7. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Miki I, Nakamura T, Kuwahara A, Yamamori M, Nishiguchi K, Tamura T, Okuno T, Omatsu H, Mizuno S, Hirai M, Azuma T, Sakaeda T. THRB Genetic Polymorphisms Can Predict Severe Myelotoxicity after Definitive Chemoradiotherapy in Patients with Esophageal Squamous Cell Carcinoma. Int J Med Sci 2012; 9(9):748-756. doi:10.7150/ijms.5081. Available from

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Objective: Chemotherapy-related toxicities are difficult to predict before treatment. In this study, we investigated whether thyroid hormone receptor beta (THRB) genetic polymorphisms can serve as a potential biomarker in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Forty-nine Japanese patients with ESCC who received a definitive chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin in conjunction with concurrent irradiation were retrospectively analyzed. Severe acute toxicities, including leukopenia, stomatitis, and cheilitis, were evaluated according to 6 single nucleotide polymorphisms (SNPs) in the gene; the intronic SNPs of rs7635707 G/T, rs6787255 A/C, rs9812034 G/T, and rs9310738 C/T and the SNPs in the 3′-untranslated region (3′-UTR) of rs844107 C/T and rs1349265 G/A.

Results: Distribution of the 4 intronic SNPs, but not the 2 SNPs in the 3′-UTR, showed a significant difference between patients with and without severe acute leukopenia. Stomatitis and cheilitis were not associated with any of the 6 analyzed SNPs. Frequency of haplotype of the 4 intronic SNPs reached approximately 97% with the 2 major haplotypes G-A-G-C (73.4%) and T-C-T-T (23.5%).

Conclusions: THRB intronic SNPs can provide useful information on CRT-related severe myelotoxicity in patients with ESCC. Future studies will be needed to confirm these findings.

Keywords: esophageal squamous cell carcinoma, thyroid hormone receptor beta, chemoradiotherapy, severe acute toxicity, prognosis.