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

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Author(s): Ikuya Miki, Tsutomu Nakamura, Akiko Kuwahara, Motohiro Yamamori, Kohshi Nishiguchi, Takao Tamura, Tatsuya Okuno, Hideaki Omatsu, Shigeto Mizuno, Midori Hirai, Takeshi Azuma, Toshiyuki Sakaeda

Journal: International Journal of Medical Sciences
ISSN 1449-1907

Volume: 9;
Issue: 9;
Start page: 748;
Date: 2012;
Original page

ABSTRACT
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.
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