Int J Med Sci 2012; 9(9):748-756. doi:10.7150/ijms.5081 This issue Cite
Research Paper
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.
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.