title: 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.
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/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/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.
authors.affiliation: 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Minegaki
authors.affiliation: 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.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: 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.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Omatsu
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 4. Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Nara 630-0293, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ; 5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.affiliation: 1. Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. ; 2. Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
mesh_terms: D000368:Aged; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D002945:Cisplatin; D005472:Fluorouracil
keywords: SLC23A2; biomarker; chemoradiotherapy; esophageal squamous cell carcinoma; polymorphism.