title: THRB genetic polymorphisms can predict severe myelotoxicity after definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Hideaki
authors.initials: H
authors.lastname: Omatsu
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy*; D002613:Cheilitis / Q000139:chemically induced; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D013280:Stomatitis / Q000139:chemically induced; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D037042:Thyroid Hormone Receptors beta; D002945:Cisplatin; D005472:Fluorouracil
keywords: chemoradiotherapy; esophageal squamous cell carcinoma; prognosis.; severe acute toxicity; thyroid hormone receptor beta